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Adenovirus Vascular Endothelial Growth Factor D (AdvVEGF-D) Therapy for Treatment of Refractory Angina Pectoris (ReGenHeart)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03039751
Recruitment Status : Not yet recruiting
First Posted : February 1, 2017
Last Update Posted : September 21, 2018
Sponsor:
Collaborators:
Queen Mary University of London
University College, London
Medical University of Vienna
Servicio Madrileño de Salud, Madrid, Spain
FinVector Vision Therapies Oy
Śląski Uniwersytet Medyczny w Katowicach
Rigshospitalet, Denmark
Euram Limited
Information provided by (Responsible Party):
Kuopio University Hospital

Tracking Information
First Submitted Date  ICMJE January 3, 2017
First Posted Date  ICMJE February 1, 2017
Last Update Posted Date September 21, 2018
Estimated Study Start Date  ICMJE February 2019
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 30, 2017)
  • Functional capacity at 6 months [ Time Frame: 6 months after gene transfer ]
    Improvement of exercise capacity 6 months after the treatment as measured by 6 minute walking test (walking distance in meters)
  • Severity of angina pectoris symptoms at 6 months [ Time Frame: 6 months after gene transfer ]
    Relieve of angina symptoms 6 months after the treatment (CCS class)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03039751 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2017)
  • Functional capacity at 12 months [ Time Frame: 12 months after gene transfer ]
    Improvement of exercise capacity 12 months after the treatment as measured by a 6 minute walking test (walking distance in meters)
  • Severity of angina pectoris symptoms at 12 months [ Time Frame: Time Frame: 12 months after gene transfer ]
    Relieve of angina symptoms 12 months after the treatment (CCS class)
  • Myocardial perfusion at 6 months [ Time Frame: 6 months after gene transfer ]
    Improvement of myocardial perfusion (myocardial perfusion reserve, MPR) at 6 months assessed with positron emission tomography (PET) or single-photon emission computed tomography (SPECT)
  • Quality of Life (EQ-5) at 6 and 12 months [ Time Frame: 6 and 12 months after gene transfer ]
    Improvement of QoL assessed with EQ-5 score with three levels of severity and visual analogue scale (VAS) at 6 and 12 months
  • Quality of Life (Short-Form Health Survey) at 6 and 12 months [ Time Frame: 6 and 12 months after gene transfer ]
    Improvement of QoL assessed with Short-Form Health Survey (SF-36) score at 6 and 12 months
  • Quality of Life (Seattle Angina Questionnaire ) at 6 and 12 months [ Time Frame: 6 and 12 months after gene transfer ]
    Improvement of QoL assessed with Seattle Angina Questionnaire score at 6 and 12 months
  • Angina pectoris medication at 6 and 12 months [ Time Frame: 6 and 12 months after gene transfer ]
    Use of short-acting nitrates to relieve symptoms of angina pectoris at 6 and 12 months (number of oral/sublingual nitrate tablets or nitrate spray inhalations during the preceding 4 weeks).
  • Adverse cardiac events at 6 and 12 months [ Time Frame: 6 and 12 months after gene transfer ]
    Incidence of cardiovascular death, myocardial infarction, stroke, revascularization or hospital admission due to coronary artery disease and a combined endpoint of Major Adverse Cardiac Events MACE (combined endpoint of cardiovascular death, myocardial infarction, stroke, revascularization or hospital admission due to coronary artery disease) at 6 and 12 months.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Adenovirus Vascular Endothelial Growth Factor D (AdvVEGF-D) Therapy for Treatment of Refractory Angina Pectoris
Official Title  ICMJE Clinical Development and Proof of Principle Testing of New Regenerative Adenovirus Vascular Endothelial Growth Factor (VEGF-D) Therapy for Cost-effective Treatment of Refractory Angina. A Phase II Randomized, Double-blinded, Placebo-controlled Study (ReGenHeart)
Brief Summary The purpose of the study is to evaluate the safety and efficacy of catheter mediated endocardial adenovirus-mediated vascular endothelial growth factor-D (AdVEGF-D) regenerative gene transfer in patients with refractory angina to whom revascularisation cannot be performed.
Detailed Description

Study overview:

The purpose of the study is to evaluate the safety and efficacy of catheter mediated AdVEGF-D regenerative gene transfer in patients with refractory angina to whom revascularisation cannot be performed.

Primary objectives:

To test the efficacy of the therapy to improve functional capacity using 6 minute walking test after 6 months follow-up and improvement of symptoms assessed by Canadian Cardiovascular Society (CCS) class.

Secondary objectives:

Efficacy of the gene transfer to increase to improve functional capacity using 6 minute walking test and improvement of symptoms assessed by CCS class after 12 months as well as increase in myocardial perfusion assessed 6 months after the gene transfer. In addition, at 6 and 12 months timepoints, the improvement quality of life (QoL), the use of angina pectoris medication, major adverse cardiac events related to coronary artery disease (cardiovascular death, myocardial infarction, stroke, revascularization and hospital admission due to coronary artery disease) or a combined endpoint of the above (Major Adverse Cardiac Events, MACE) will be evaluated.

Study design:

ReGenHeart is a randomized, double-blinded, placebo-controlled multicentre phase II study which will be conducted at 6 centers. The study will evaluate the efficacy and safety of catheter mediated endocardial AdVEGF-D regenerative gene transfer in 180 patients with angina pectoris or equivalent symptom despite optimal medical therapy and who are not suitable candidates for coronary revascularization with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) (refractory angina patients).

Study population:

180 patients will be recruited from the six centers in 2 years. The patients will be selected for the trial on the basis of medical history, general status, laboratory analyses, coronary angiogram and 6-minute walking test. Patients with CCS 2-3 angina pectoris despite optimal medical therapy and who are not eligible for coronary angioplasty or bypass operation due to diffuse coronary stenosis, small coronary vessels, repeated revascularization or too high risk for operation, will be included.

The number of subjects to be recruited and randomized to the trial will be 180 (2:1 ratio to the treatment and control groups).

Investigational drug product:

First generation replication-deficient AdVEGF-D produced in 293 cells will be injected into ten sites in the endocardium. The dose of 1x1011 vp in a total volume of 2 ml (10 times 0.2 ml) will be used. Control patients will be treated and operated exactly in the same way except that placebo (buffer solution without gene) injection into the myocardium is used.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Refractory Angina Pectoris
  • Gene Transfer
  • Coronary Artery Disease
Intervention  ICMJE
  • Drug: AdvVEGF-D
    AdvVEGF-D will be injected into 10 sites of the myocardium
  • Drug: Control Rx
    Placebo (buffer solution without gene) will be injected into 10 sites of the myocardium
Study Arms  ICMJE
  • Experimental: AdvVEGF-D
    Intramyocardial AdVEGF-D
    Intervention: Drug: AdvVEGF-D
  • Placebo Comparator: Control
    Intramyocardial placebo (buffer solution without gene)
    Intervention: Drug: Control Rx
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: January 30, 2017)
180
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • informed consent signed
  • age > 30 but < 85 years
  • significant angina pectoris (CCS 2-3) despite of optimal medication
  • significant stenosis (> 60%) in coronary angiography (< 6 months)
  • contraindication to CABG or PCI due to diffuse or distal stenosis, chronic total occlusion, vessels with difficult anatomy, stenosis with severe calcifications and stenosis in small vessels (<2.5 mm))
  • angina pectoris or equivalent symptoms in the 6-minute walking exercise test
  • left ventricle wall > 8 mm detected by transthoracic echocardiography or magnetic resonance imaging (treatment area)

Exclusion Criteria:

  • women in fertile age
  • diabetes mellitus with severe complications such as diabetic retinopathy or nephropathy
  • clinically significant anemia (hemoglobin count < 120 mg/l in male, < 110 mg/l in female; hematocrit < 0.36), leukopenia (b-leukocyte count < 3.0x109/l), leukocytosis (b-leukocyte count > 12.0x109/l) or thrombocytopenia (b-thrombocyte count < 100x109/l)
  • renal insufficiency (P-creatinine > 160 mg/l)
  • liver insufficiency (P-alanine aminotransferase or P-alkaline phosphatase over 2 x normal)
  • haematuria of unknown origin
  • severe hypertension (systolic blood pressure > 200 mmHg or diastolic blood pressure > 110 mmHg) or significant hypotension (systolic blood pressure < 90 mmHg)
  • significant obesity (Body Mass Index > 35)
  • acute infection
  • immunosuppressive medication
  • significant impairment of left ventricular function (ejection fraction < 25% in echocardiography)
  • symptomatic congestive heart failure (New York Heart Association class 3-4)
  • haemodynamically significant (grade 3-4/4) aortic or mitral regurgitation or other heart disease needing surgery
  • recent (< 6 weeks) acute coronary syndrome or myocardial infarction, PCI or CABG, stroke or transient ischemic attack (TIA)
  • current or suspected malignancy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Juha EK Hartikainen, professor +358447113945 juha.hartikainen@kuh.fi
Contact: Seppo Ylä-Herttuala, professor +358505924067 seppo.ylaherttuala@uef.fi
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03039751
Other Study ID Numbers  ICMJE KUH5101111
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Data wil be shared to Partners of ReGenHeart Consortium
Responsible Party Kuopio University Hospital
Study Sponsor  ICMJE Kuopio University Hospital
Collaborators  ICMJE
  • Queen Mary University of London
  • University College, London
  • Medical University of Vienna
  • Servicio Madrileño de Salud, Madrid, Spain
  • FinVector Vision Therapies Oy
  • Śląski Uniwersytet Medyczny w Katowicach
  • Rigshospitalet, Denmark
  • Euram Limited
Investigators  ICMJE
Study Director: Seppo Ylä-Herttuala Kuopio University Hospital
PRS Account Kuopio University Hospital
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP